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Biomedical subjects

M J Edwards

Publications and source records attributed to M J Edwards.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reliable lymphatic drainage to axillary sentinel lymph nodes regardless of tumor location within the breast.

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.

Axilla↗
PubMed2001

The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer.

BACKGROUND: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases. METHODS: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining. RESULTS: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were "upstaged" by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen. CONCLUSIONS: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.

Axilla↗
PubMed2001

Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.

BACKGROUND: Intraoperative frozen section pathologic analysis of sentinel lymph node (SLN) may guide immediate (single-stage) completion axillary dissection for patients with nodal metastases. METHODS: The results of 203 consecutive patients undergoing SLN biopsy who had intraoperative pathology consultation between January 1998 and September 2000 were reviewed. SLN were analyzed by standard frozen section procedures. Final pathologic analysis included hematoxylin and eosin (H&E) staining of serial sections at 2-mm intervals. RESULTS: Frozen section analysis correctly identified a positive or negative result in 185 of 203 cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor by frozen section, but positive on permanent section analysis (sensitivity 68%). The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to have true positive and false negative results, respectively (P <0.003). A single false positive SLN is reported. CONCLUSIONS: Two thirds of the patients were spared the need for reoperative axillary lymphadenectomy.

Aged↗
PubMed2001

Radiofrequency ablation for unresectable hepatic tumors.

BACKGROUND: Radiofrequency ablation (RFA) is a relatively new treatment for unresectable hepatic tumors. The purpose of this analysis was to examine the frequency of complications and local recurrence associated with RFA. METHODS: Patients who underwent RFA of hepatic tumors with curative intent were included in this study. At laparotomy, RFA was performed using intraoperative ultrasound guidance. Computed tomography scans were obtained in the immediate postoperative period and every 3 to 6 months thereafter. RESULTS: Forty patients underwent RFA for 122 hepatic tumors. Thirty-one patients had metastatic lesions from colorectal cancer; 9 had other liver tumors. Complications occurred in 8 patients. With 9.5 months median follow-up, 6 patients had local recurrence of their ablated tumors. CONCLUSIONS: Our initial experience shows that RFA can effectively eradicate unresectable hepatic tumors. The rate and severity of complications appear acceptable. However, further study is necessary to assess long-term recurrence rates and effect on overall survival.

Catheter Ablation↗
PubMed2001

Increasing the efficiency of virus infectivity assays: small inoculum volumes are as effective as centrifugal enhancement.

Improving the virus particle:infectious unit ratio is a continuing goal for animal virologists. It is demonstrated for an influenza A virus that decreasing the size of the inoculum volume to 10 microl per well of a 96-well plate was as effective as using centrifugal force with inoculum up to 250 microl. Both achieved a 7.5-fold increase in infectivity in monolayers of MDCK cells compared with standard conditions. The underlying principle of both methods is to bring virus particles into close contact with cell receptors.

Animals↗
PubMed2001

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate.

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Breast Neoplasms↗
PubMed2001

Reversible posterior leukoencephalopathy syndrome following CHOP chemotherapy for diffuse large B-cell lymphoma.

A 63-year-old female with stage IE diffuse large B-cell lymphoma developed reversible posterior leukoencephalopathy syndrome (RPLS) following CHOP chemotherapy, with typical clinical and radiological findings. RPLS is a rare neurological syndrome characterised by visual disturbances, seizures, headaches and altered conscious level which has been associated with malignant hypertension, pre-eclampsia and some drugs, including ciclosporin. It has not been previously reported following CHOP chemotherapy. Alternative treatment should be considered for patients who develop this rare complication.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

SAP controls T cell responses to virus and terminal differentiation of TH2 cells.

SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), is altered in patients with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon-gamma-producing spleen and liver cells compared to wild-type mice. The immune responses of SAP-deficient mice to infection with Leishmania major together with in vitro studies showed that activated SAP-deficient T cells had an impaired ability to differentiate into T helper 2 cells. The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which explains in part the complexity of the XLP phenotypes.

Animals↗
PubMed2001

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

Adolescent↗
PubMed2001

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Breast Neoplasms↗
PubMed2001

Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques.

OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.

Breast Neoplasms↗
PubMed2001

Routine cervical spine radiography for trauma victims: Does everybody need it?

OBJECTIVE: The purpose of this study was to evaluate the indication for routine cervical spine radiography in trauma patients. METHODS: Prospective analysis of radiologic and clinical findings was performed during a 5-year period. Patients suitable for a clinical decision rule were reviewed separately. RESULTS: Of the 1,757 consecutive patients included in the study, 38 were diagnosed with a cervical spine injury. Of the 599 patients suitable for the clinical decision rule, 62 had midline cervical tenderness, including 2 with cervical spine injury. No additional cervical spine injuries were found during follow-up. CONCLUSION: It is within good practice, and it is also cost-effective, to obtain a cervical spine radiograph only on clinical parameters in trauma patients with no apparent bodily trauma and optimal parameters. With this clinical decision rule, 30.6% of all cervical spine series were redundant, and no (occult) spinal fractures would have been undetected.

Adolescent↗
PubMed2001

A haemagglutinin (HA1)-specific FAb neutralizes influenza A virus by inhibiting fusion activity.

H9-D3-4R2 (referred to as H9), a murine monoclonal HA1-specific IgG3, recognizes an epitope within antigenic site Cb of influenza virus A/PR/8/34 (H1N1). At 50% neutralization, inhibition of virus-mediated fusion was responsible for the majority of neutralization but, at higher antibody concentrations, the attachment of virus to target cells was also inhibited and may have contributed to neutralization. H9 FAb was also neutralizing, although the concentration needed was two orders of magnitude greater than for the IgG. Functional affinity of the IgG and affinity of the FAb were almost identical, and it is not clear why the neutralization efficiency of the FAb was so low. Unlike its IgG, H9 FAb had no detectable effect on virus attachment but inhibited virus fusion activity. It thus appears that monovalent binding by this antibody is sufficient to inhibit fusion activity and that this was directly responsible for neutralization of infectivity.

Animals↗
PubMed2001

Hemagglutinin 1-specific immunoglobulin G and Fab molecules mediate postattachment neutralization of influenza A virus by inhibition of an early fusion event.

In standard neutralization (STAN), virus and antibody are reacted together before inoculation of target cells, and inhibition of almost any of the processes concerned in the early interaction of virus and cell, including inhibition of virus attachment to cell receptors, can be the cause of neutralization by a particular monoclonal antibody (MAb). To simplify the interpretation of antibody action, we carried out a study of postattachment neutralization (PAN), where virus is allowed to attach to target cells before neutralizing antibody is introduced. We used influenza virus A/PR/8/34 (H1N1) and monoclonal immunoglobulin G (IgG) molecules and their Fabs specific to antigenic sites Sb (tip), Ca2 (loop), and Cb (hinge) of the hemagglutinin 1 (HA1) protein. All IgGs and Fabs gave PAN, although with reduced efficiency compared with STAN. Thus, bivalent binding of antibody was not essential for PAN. By definition, none of these MAbs gave PAN by inhibiting virus attachment, and they did not elute attached virus from the target cell or inhibit endocytosis of virus. However, virus-cell fusion, as demonstrated by R18 fluorescence dequenching or hemolysis of red blood cells, was inhibited in direct proportion to neutralization and in a dose-dependent manner and was thus likely to be responsible for the observed neutralization. However, to get PAN, it was necessary to inhibit the activation of the prefusion intermediate, the earliest known form on the fusion pathway that is created when virus is incubated at pH 5 and 4 degrees C. PAN antibodies may act by binding HA trimers in contact with the cell and/or trimers in the immediate vicinity of the virus-cell contact point and so inhibit the recruitment of additional receptor-HA complexes.

Animals↗
PubMed2001

STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia.

Members of the signal transducer and activator of transcription (STAT) family are transcription factors that mediate many of the effects of pro- and anti-inflammatory cytokines. The progressive systemic inflammatory response induced by endotoxin is mediated by overzealous cytokine production. Here we identify STAT4 and STAT6 as critical regulators of the systemic inflammatory response to endotoxin. Mice deficient for STAT4 or STAT6 were highly susceptible to lethal endotoxemia. In STAT4(-/-) mice, antibody blockade of IL-12 prevented mortality, suggesting that STAT4 confers protection, while another signaling pathway mediates the detrimental effects of IL-12. In STAT6(-/-) mice we observed dysregulated activation of the transcription factor NF-kappaB, resulting in augmented production of proinflammatory cytokines and chemokines. Furthermore, STAT6(-/-) mice displayed increased organ accumulation of leukocytes and significant hepatocellular injury. These findings demonstrate that STAT4 and STAT6 confer protection against endotoxin-induced death and that for STAT6 these protective effects occur through the regulation of NF-kappaB activation and subsequent production of proinflammatory cytokines and chemokines.

Animals↗
PubMed2001

Associations between the Holden Psychological Screening Inventory and the Personality Assessment Screener in a nonclinical sample.

Associations between two screening inventories of psychopathology were investigated using a sample of 156 first-year undergraduates. Analyses supported the reliability and validity of all Holden Psychological Screening Inventory scales, but only of some of the Personality Assessment Screener scales. Orthogonal dimensions of Depression, General Distress, and Antisocial Tendencies represented the common latent structure of the two inventories.

Adult↗
PubMed2001

Histoplasmosis as an isolated liver lesion: review and surgical therapy.

Histoplasmosis is the most common cause of fungal infection in the Ohio River Valley of the United States. Ninety-nine per cent of patients exposed to histoplasmosis develop only subclinical infections. Liver involvement is common in disseminated histoplasmosis, which usually originates in the lungs. There has been only one prior case described in the literature of histoplasmosis presenting as an isolated liver mass. We report a rare case that presented as a solitary right-sided liver lesion invading the diaphragm, with review of the literature for therapy of histoplasmosis of the liver.

Adult↗